Dimethyl fumarate and vaccination regimens

Abstract

Provided herein is a method of treating or preventing a disease or disorder (e.g., MS) in a subject in need thereof, comprising (a) administering to the subject a first dose of a pharmaceutical composition comprising a fumarate agent (e.g., DMF) for a first dosing period; (b) administering a vaccine; and (c) administering to the subject a second dose of the pharmaceutical composition for a second dosing period.

What is claimed is: 
     
       1. A method of treating multiple sclerosis in a human subject in need thereof, said method comprising:
 (a) administering to the subject a first dose of a pharmaceutical composition for a first dosing period, wherein the pharmaceutical composition comprises a fumarate agent selected from the group consisting of monomethyl fumarate, a pharmaceutically acceptable salt of monomethyl fumarate, dimethyl fumarate, and a combination thereof; 
 (b) administering a vaccine to the subject, wherein the subject receives the vaccine during the first dosing period; and 
 (c) administering to the subject a second dose of the pharmaceutical composition for a second dosing period, wherein: (i) the second dosing period is after the first dosing period, and (ii) the second dosing period is initiated within one day of the end of the first dosing period; 
 wherein the second dose is the same as the first dose, and the first dose and the second dose are administered daily; 
 wherein the multiple sclerosis is a relapsing form of multiple sclerosis; 
 wherein the vaccine is an inactive vaccine; 
 wherein the first dose is a therapeutically effective amount of monomethyl fumarate, a pharmaceutically acceptable salt of monomethyl fumarate, dimethyl fumarate, or a combination thereof; and 
 wherein the method further comprises 10 minutes to an hour before said administering step (a), or 10 minutes to an hour before said administering step (c), a step of administering to the subject a non-steroidal anti-inflammatory drug. 
 
     
     
       2. The method of  claim 1 , wherein the fumarate agent is dimethyl fumarate. 
     
     
       3. The method of  claim 2 , wherein the first dose is a daily amount of about 480 mg dimethyl fumarate. 
     
     
       4. The method of  claim 1 , further comprising administering a titration dose of the fumarate agent prior to the first dosing period. 
     
     
       5. The method of  claim 4 , wherein the fumarate agent is dimethyl fumarate and the titration dose is a daily amount of about 240 mg dimethyl fumarate. 
     
     
       6. The method of  claim 1 , wherein the pharmaceutical composition is in the form of a capsule or tablet. 
     
     
       7. The method of  claim 2 , wherein the dimethyl fumarate is in the form of microtablets or micropellets, and wherein the microtablets or micropellets are enterically coated. 
     
     
       8. The method of  claim 7  wherein the microtablets or micropellets are contained in a capsule. 
     
     
       9. The method of  claim 1 , wherein the vaccine induces a T cell-dependent immune response. 
     
     
       10. The method of  claim 9 , wherein the vaccine induces a T cell-dependent anamnestic humoral immune response. 
     
     
       11. The method of  claim 9 , wherein the vaccine induces a T cell-dependent neoantigen immune response. 
     
     
       12. The method of  claim 1 , wherein the vaccine induces a T cell-independent immune response. 
     
     
       13. The method of  claim 1 , wherein the vaccine is a vaccine selected from the group consisting of tetanus diphtheria toxoids vaccine, keyhole limpet hemocyanin vaccine, pneumovax-23 vaccine, and a combination thereof. 
     
     
       14. The method of  claim 13 , wherein the vaccine is tetanus diphtheria toxoids vaccine. 
     
     
       15. The method of  claim 13 , wherein the vaccine is keyhole limpet hemocyanin vaccine. 
     
     
       16. The method of  claim 13 , wherein the vaccine is pneumovax-23 vaccine. 
     
     
       17. The method of  claim 1 , wherein the vaccine is meningococcal polysaccharide diphtheria conjugate vaccine quadrivalent. 
     
     
       18. The method of  claim 1 , wherein the multiple sclerosis is relapsing-remitting multiple sclerosis. 
     
     
       19. The method of  claim 1 , wherein the multiple sclerosis is secondary progressive multiple sclerosis. 
     
     
       20. The method of  claim 3 , further comprising administering a titration dose of the fumarate agent prior to the first dosing period. 
     
     
       21. The method of  claim 20 , wherein the titration dose is a daily amount of about 240 mg dimethyl fumarate. 
     
     
       22. The method of  claim 1 , wherein the fumarate agent is monomethyl fumarate. 
     
     
       23. The method of  claim 1 , wherein the fumarate agent is a pharmaceutically acceptable salt of monomethyl fumarate. 
     
     
       24. The method of  claim 1 , wherein the non-steroidal anti-inflammatory drug is selected from the group consisting of aspirin, ibuprofen, naproxen, ketoprofen, celecoxib, and a combination thereof. 
     
     
       25. The method of  claim 24 , wherein the non-steroidal anti-inflammatory drug is aspirin. 
     
     
       26. The method of  claim 25 , wherein the aspirin is administered 30 minutes before said administering step (a), or 30 minutes before said administering step (c).